Using transcranial magnetic stimulation to study corticospinal excitability, provide biomarkers of disease progression and understand the effects of fitness and exercise training in Multiple Sclerosis

Chaves, Arthur R. de A. (2020) Using transcranial magnetic stimulation to study corticospinal excitability, provide biomarkers of disease progression and understand the effects of fitness and exercise training in Multiple Sclerosis. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Multiple Sclerosis (MS) is an immune-mediated inflammatory neurodegenerative disease, affecting both white and gray matter, leading to physical and cognitive dysfunction. Exacerbation of symptoms, caused by intensification of neuroinflammation, is characteristic of the relapsing-remitting type of MS while neurodegeneration is more typical of progressive stages. Because of the complexity of the disease, biomarkers are being sought to track progression and observe the benefits of treatments that aim to repair or protect the central nervous system. In my doctoral work, I used Transcranial Magnetic Stimulation (TMS), a tool that measures corticospinal excitability (CSE), to investigate biomarkers of MS progression, and to understand whether superior fitness and exercise training would positively impact these biomarkers. In my first study, I demonstrated that people with MS have alarmingly low cardiorespiratory fitness which was associated with increasing intracortical inhibition, a biomarker of diminished neuroplasticity. Such inhibition was also associated with fatigue, one of the most troubling symptoms experienced by people with MS. In the second study, I investigated the patterns of how MS affected each brain hemisphere and revealed that early in the disease, people with MS seem to have paradoxically higher excitability in the hemisphere corresponding to the weaker hand. This suggested that the central nervous system may be in a state of hyperexcitability which I could detect using TMS. In the next two studies, I investigated the acute and long-term (12 weeks) effects of exercise on CSE among people with progressive MS. An acute bout of exercise was accompanied by increased excitation and reduction in inhibition but mainly in the hemisphere corresponding to the stronger hand. Those who were fitter had more robust benefits. After 12 weeks (3x/week) of walking exercise training, CSE enhanced bilaterally. Importantly, all CSE enhancements were short term and returned to baseline 3 months after cessation of the exercise training. The results of my doctoral work support the use of TMS to investigate CSE and provide biomarkers of central nervous system integrity in MS. More importantly, these results demonstrated that sedentarism can negatively affect the MS brain, and that performing exercise can potentiate cortical mechanisms related to enhanced neuroplasticity.

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